The utilization of nanotechnology in the female reproductive system and related disorders.

The health of the reproductive system is intricately linked to female fertility and quality of life. There has been a growing prevalence of reproductive system disorders among women, particularly in younger age groups, resulting in significant adverse effects on their reproductive health. Consequently, there is an urgent need for effective treatment modalities. Nanotechnology, as an advanced discipline, provides innovative avenues for managing and treating diseases of the female reproductive system by enabling precise manipulation and regulation of biological molecules and cells. By utilizing nanodelivery systems, drugs can be administered with pinpoint accuracy, leading to reduced side effects and improved therapeutic efficacy. Moreover, nanomaterial imaging techniques enhance diagnostic precision and sensitivity, aiding in the assessment of disease severity and progression. Furthermore, the implementation of nanobiosensors facilitates early detection and prevention of ailments. This comprehensive review aims to summarize recent applications of nanotechnology in the treatment of female reproductive system diseases. The latest advancements in drug delivery, diagnosis, and treatment approaches will be discussed, with an emphasis on the potential of nanotechnology to improve treatment outcomes and overall quality of life.

Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of asparagus against polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age that still lacks effective treatment. Inflammation is one of the important features of PCOS. Asparagus (ASP) has anti-inflammatory, antioxidant, and anti-aging pharmacological effects, and its anti-tumor effects have been demonstrated in a variety of tumors. However, the role and mechanism of ASP in PCOS remain unclear. METHODS: The active components of ASP and the key therapeutic targets for PCOS were obtained by network pharmacology. Molecular docking was used to simulate the binding of PRKCA to the active components of ASP. The effects of ASP on inflammatory and oxidative stress pathways in PCOS, and the regulation of PRKCA were examined by KGN, a human derived granulosa cell line. PCOS mouse model validated the results of in vivo experiments. RESULTS: Network pharmacology identified 9 major active ingredients of ASP with 73 therapeutic targets for PCOS. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment yielded 101 PCOS-related signaling pathways. The hub gene PRKCA was obtained after taking the gene intersection of the top 4 pathways. Molecular docking showed the binding of PRKCA to the 7 active components in ASP. In vitro and in vivo experiments showed that ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects. ASP can partially restore the low expression of PRKCA in the PCOS models. CONCLUSION: The therapeutic effect of ASP on PCOS is mainly achieved by targeting PRKCA through the 7 active components of ASP. Mechanistically, ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects, and PRKCA was its potential target.

Management of candiduria in hospitalized patients: a single-center study on the implementation of IDSA guidelines and factors affecting clinical decisions.

Candiduria are common findings in clinic especially in hospitalized patients, while its significance remains undetermined. Since there are few criteria to follow, physicians tended to make decisions by personal experience in many cases in clinical practice. The present study was designed to unveil the present situation of candiduria management in hospitalized patients in clinical practice. A total of 251 hospitalized candiduria patients were retrospectively enrolled in the study. Clinical data on patient demographics, basic conditions, catheter using, urinary symptoms, laboratory data, and antifungal therapies were obtained from electronic medical records. The high rate of the candiduria cases were managed inappropriately after the introduction of the Infectious Diseases Association of America (IDSA) evidence-based recommendations, both in the management of urinary catheter and antifungal agents. Overtreatment was common in asymptomatic candiduria patients. For symptomatic patients, improper drug selections were not rare. In addition, a part of candiduria patients did not receive antifungal therapies although the IDSA recommends. A statistically significant difference was only found in hospital charges of symptomatic candiduria patients managed following IDSA or not. The recurrence rate, mortality, and hospital stay length were similar in candiduria patients regardless of the clinical management. Physicians tend to start empiric antifungal therapy for candiduria patients with pneumonia, multisite of Candida colonization, higher urine Candida CFUs, and long hospital stay. Candiduria has not received special attention today, and empirical antifungal treatment is common. IDSA guidelines are important to standardize the management of candiduria in clinic; however, the significance of the guidelines needs to be further clarified in future multicenter investigations.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits.

OBJECTIVE: To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. METHODS: In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. RESULTS: For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. CONCLUSION: Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection.

Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice.

CD4(+) T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN-gamma in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-gamma, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17(-/-) mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology.

Efficient adenovirus-mediated gene transfer to gastric tissue by oral administration.

BACKGROUND: Recombinant adenoviruses (rAd) are well-characterized viral vectors and have been studied in many human diseases. However, there are no detailed methods for transferring genes to the stomach using rAd. METHODS: Gastric epithelial cells were infected with rAd encoding green fluorescence protein (AdGFP) for different times, or with AdGFP that had been incubated in artificial gastric juice at different pH values for 1 h. Gene expression was detected by fluorescence microscope and flow cytometry. Mice were infected via oral administration with rAd encoding red fluorescence protein and beta-galactosidase (AdRFP-lacZ) or rAd encoding mouse interleukin-17 (AdmIL-17), and tissues were collected at the indicated times after infection. LacZ expression in different tissues was detected by X-gal staining and IL-17 expression in the stomach was assessed by the real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. Inflammation in the stomach was also assessed. RESULTS: rAd could infect the gastric epithelial cells and tolerate pH 5 for 1 h in vitro. Adenovirus-mediated genes were specifically expressed in the gastrointestinal tract and transgene expression persisted in gastric tissue for up to 7 days after oral administration of AdRFP-lacZ. Oral administration of AdmIL-17 induced mIL-17 expression in gastric tissue at the mRNA and protein levels and protein level peaked on day 5 post-infection. IL-6, a target protein of IL-17, and gastric inflammation also increased in AdmIL-17-infected mice. CONCLUSIONS: The present study has established a detailed method for transferring adenovirus-mediated gene to the stomach, which may provide a valuable approach for gene therapy or the study of the basic biology of gastric diseases.

Identification of small noncoding RNAs in Helicobacter pylori by a bioinformatics-based approach.

Small noncoding RNAs (sRNAs) are a group of regulatory RNA molecules normally without a protein-coding function. In recent years, the importance of sRNAs as mediators of gene expression in bacteria has begun to be recognized. More than 70 sRNAs have been known in Escherichia coli. However, little is known about sRNAs in Helicobacter pylori, a human pathogen associated with gastric diseases. Here, we systematically identified sRNAs in the H. pylori genome by a computational approach based on gene location, sequence conservation, promoter and terminator search, and secondary structure. Among a total of six candidate sRNAs initially predicted, two novel sRNAs (IG-443 and IG-524) were confirmed by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). Virtually, they were a class of natural antisense transcripts, which were complementary to partial sequences of the following genes: flagellar motor switch gene (fliM) and fumarase (fumC). Taken together, the results indicate that there exist novel sRNAs in H. pylori and these RNAs might play a potential role in regulating gene expression.

Psychological stress enhances the colonization of the stomach by Helicobacter pylori in the BALB/c mouse.

Helicobacter pylori infection is a risk factor for development of peptic ulcers, and psychological stress (PS) may have a role in the pathogenesis of this condition. However, no interaction between PS and H. pylori infection (HI) has been established in the development of peptic ulcer, because colonization by H. pylori is the first step in the infection of the gastric mucosa, we examined H. pylori colonization of the stomach in BALB/c mice after PS. The mice were subjected to PS in a communication box test, in which they observed other mice experiencing a physical stressor (electrical) before they were inoculated with H. pylori. We found that the H. pylori colonization in the stomach of psychologically stressed mice was significantly greater than in the control mice (P < 0.05), and histological examination showed that the gastric mucosal injury in the stressed mice was more extensive than in the control mice (P < 0.05). To explore the underlying mechanisms, we administered RU486 (a type II glucocorticoid (GC) receptor antagonist) to antagonize the effect of endogenous corticosterone: this treatment decreased colonization by H. pylori in the psychologically stressed mice. We conclude that HI of the stomach of BALB/c mice is enhanced by PS, and the effect may be mediated by GCs.